Methanol → HCID 86731025, compound

HRID 2280211Notes

Reaction equation

HRID 2280211 reaction equation
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].C(Cl)Cl.[NH2:16][C:17]1[S:29][C:28]2[CH2:27][C@@H:26]3[C@H:21]([CH2:22][C@@H:23]([C:31]([N:33]([CH2:42][CH2:43][CH3:44])[C:34]([NH:36][CH2:37][CH2:38][N:39]([CH3:41])[CH3:40])=[O:35])=[O:32])[CH2:24][N:25]3[CH3:30])[CH2:20][C:19]=2[C:18]=1[C:45]#[N:46].[CH3:47][OH:48]>CN(C)C1C=CN=CC=1>[C:45]([C:18]1[C:19]2[CH2:20][C@@H:21]3[C@@H:26]([CH2:27][C:28]=2[S:29][C:17]=1[NH:16][C:1](=[O:2])[O:48][CH3:47])[N:25]([CH3:30])[CH2:24][C@H:23]([C:31]([N:33]([C:34](=[O:35])[NH:36][CH2:37][CH2:38][N:39]([CH3:41])[CH3:40])[CH2:42][CH2:43][CH3:44])=[O:32])[CH2:22]3)#[N:46]

Participants

6

Reactant 4

HCID 887MethanolHCID 6344DichloromethaneHCID 682631,1'-Carbonyldiimidazole3×HCID 665485291399442-97-7

Product 1

HCID 86731025HCID 86731025, compound

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst3×

Procedure

To a mixture of 1,1′-carbonyldiimidazole (13 mg) and methylene chloride (1 mL) was added 4-dimethylaminopyridine (8 mg), followed by 1-{[(4aR*,6R*,8aR*)-2-amino-3-cyano-8-methyl-4H,4aH,5H,6H,7H,8H,8aH,9H-thieno[3,2-g]quinolin-6-yl]carbonyl}-3-[2-(dimethylamino)ethyl]-1-propylurea (example 1-15) (30 mg) while stirring under ice bath cooling, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture was added 1,1′-carbonyldiimidazole (13 mg), followed by 4-dimethylaminopyridine (8 mg) and warmed to room temperature and stirred for 1 hour. To the reaction mixture was added 1,1′-carbonyldiimidazole (50 mg), followed by 4-dimethylaminopyridine (32 mg) while stirring at room temperature and stirred at the same temperature for 12 hours. To the reaction mixture was added methanol (0.003 mL) while stirring at room temperature and stirred at the same temperature for 1 hour. The mixture was purified by aminopropyl silica gel column chromatography (eluent: 0%-10% methanol/methylene chloride, gradient elution) to give the title compound (18 mg). The structure was illustrated in Table 11.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at the same temperature for 1 hour
  3. stirringstirred for 1 hour
  4. stirringwhile stirring at room temperature
  5. stirringstirred at the same temperature for 12 hours
  6. stirringwhile stirring at room temperature
  7. stirringstirred at the same temperature for 1 hour
  8. customThe mixture was purified by aminopropyl silica gel column chromatography (eluent: 0%-10% methanol/methylene chloride, gradient elution)

Sources & evidence

ORD record
ord-52ffe9ab81a84773819f572c3b625c08
Source dataset
uspto-grants-2015_09
Patent number
US09138434B2

Reaction notes

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